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Research into the development of stem cell-derived (SCD) gametes in humans, otherwise known as in vitro gametogenesis (IVG), is largely motivated by reproductive aims. Especially, the goal of establishing genetic parenthood by means of SCD-gametes is considered an important aim. However, like other applications in the field of assisted reproduction, this technology evokes worries about the possibility of creating so-called ‘designer babies.’ In this paper, we investigate various ways in which SCD-gametes could be used to create such preference-matched offspring, and what this would mean for the acceptability of IVG, if it is premised that it is morally problematic to ‘design’ offspring. We argue that IVG might facilitate the creation of preference-matched offspring, but conclude that this should not undermine the moral acceptability of IVG altogether—even if one concedes the premise that creating ‘designer babies’ is morally problematic. In the light of this, we also point at a possible inconsistency for a position that condemns the creation of ‘designer offspring,’ while accepting the various endeavors to have genetically related offspring.
This article explores the ethical issues that have been identified in emerging technologies, from early genetic engineering to synthetic biology. The scientific advances in the field form a continuum, and some ethical considerations can be raised time and again when new developments occur. An underlying concern is the cumulative effect of scientific advances and ensuing technological innovation that can change our understanding of life and humanity.
Resin composite materials that are used to restore tooth cervical lesions associated with gingival recessions can hamper healing after root coverage surgeries. This study evaluates the in vitro cytotoxic effect of five resin composites (two commercial and three experimental) on oral mesenchymal stem cells (MSCs) and the persistence of stemness properties in high passage MSCs. Sorption and solubility tests were made for all materials. MSCs were isolated from re-entry palatal and periodontal granulation tissues and were characterized and cultured on composite discs. Cytotoxicity of the materials was evaluated by the Alamar Blue viability test, by Paul Karl Horan (PKH) labeling, and by immunocytochemical staining for actin. Water and saliva sorption and solubility data revealed that two of the experimental materials behaved comparable with the marketed resin composites. The Alamar Blue viability test shows that both cell lines grew well on composite discs that seemed to induce no apparent toxic effects. No signs of disruption of cytoskeleton organization was seen. Experimental resin composites can be recommended for further investigation for obtaining approval for use. The standard minimal criteria were fulfilled for high passage MSCs. Palatal tissue regains its regenerative properties in terms of MSC presence in the re-entry area after 6 months of healing.
To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy.
Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted.
Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site.
The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.
There is growing evidence that the cells in the maculae flavae are tissue stem cells of the human vocal fold mucosa, and that the maculae flavae are a candidate for a stem cell niche. The role of microenvironment in the maculae flavae of the human vocal fold mucosa was investigated.
Anterior maculae flavae from six surgical specimens were cultured in a mesenchymal stem cell growth medium or a Dulbecco's modified Eagle's medium.
Using mesenchymal stem cell growth medium, the subcultured cells formed a colony-forming unit, and cell division reflected asymmetric self-renewal. This indicates that these cells are mesenchymal stem cells or stromal stem cells in the bone marrow. Using Dulbecco's modified Eagle's medium, the subcultured cells showed symmetric cell division without a colony-forming unit.
A proper microenvironment in the maculae flavae of the human vocal fold mucosa is necessary to be effective as a stem cell niche that maintains the stemness of the contained tissue stem cells.
There is growing evidence to suggest that cells in the maculae flavae are tissue stem cells of the human vocal fold and maculae flavae are a stem cell niche.
Three newborn vocal folds were investigated. Immunoreactivity to antibodies directed to cytokeratin, desmin, glial fibrillary acidic protein, vimentin, cluster of differentiation 34, cluster of differentiation 45, collagen type I, telomerase reverse transcriptase, SOX17 and stage-specific embryonic antigen 3 was investigated.
The cells in the newborn maculae flavae expressed haematopoietic markers (cluster of differentiation 34, cluster of differentiation 45) and collagen type I, which are the major makers of bone marrow derived circulating fibrocytes. The cells expressed epithelium, muscle, neural and mesenchymal cell associated proteins, and endodermal marker, indicating that they are undifferentiated and express proteins of all three germ layers. The cells also expressed stage-specific embryonic antigen 3 and telomerase reverse transcriptase.
The cells in the newborn maculae flavae are undifferentiated cells arising from the differentiation of bone marrow cells. The results of this study are consistent with the hypothesis that the cells in maculae flavae are tissue stem cells.
Tissue engineering using biocompatible scaffolds, with or without cells, can permit surgeons to restore structure and function following tissue resection or in cases of congenital abnormality. Tracheal regeneration has emerged as a spearhead application of these technologies, whilst regenerative therapies are now being developed to treat most other diseases within otolaryngology.
Methods and results:
A systematic review of the literature was performed using Ovid Medline and Ovid Embase, from database inception to 15 November 2014. A total of 561 papers matched the search criteria, with 76 fulfilling inclusion criteria. Articles were predominantly pre-clinical animal studies, reflecting the current status of research in this field. Several key human research articles were identified and discussed.
The main issues facing research in regenerative surgery are translation of animal model work into human models, increasing stem cell availability so it can be used to further research, and development of better facilities to enable implementation of these advances.
Vision loss caused by the death of photoreceptors is the leading cause of irreversible blindness in the developed world. Rapid advances in stem cell biology and techniques in cell transplantation have made photoreceptor replacement by transplantation a very plausible therapeutic strategy. These advances include the demonstration of restoration of vision following photoreceptor transplantation and the generation of transplantable populations of donor cells from stem cells. In this review, we present a brief overview of the recent progress in photoreceptor transplantation. We then consider in more detail some of the challenges presented by the degenerating retinal environment that must play host to these transplanted cells, how these may influence transplanted photoreceptor cell integration and survival, and some of the progress in developing strategies to circumnavigate these issues.
The aim of this study was to analyze whether the mesenchymal stromal cells (MSCs) isolated from palatal tissue grafts harvested in order to cover gingival recessions have the basic characteristics of stem cells. The palatal tissue cells were processed using a special culture medium that stimulated the development of only undifferentiated cellular lines. Cells at passage 4 were evaluated by flow cytometry to examine the expression of specific surface markers and were tested for multilineage differentiation capacity. These cells collected at passage 4 were also investigated for the capacity to cluster into embryoid body aggregates. Palatal MSCs displayed positive staining for the mesenchymal markers CD29, CD73, CD105, CD 49e, and CD44, but did not express hematopoietic markers CD34/45. The palatal MSCs successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. When seeded in special conditions, palatal MSCs propagated into unattached spheres resembling embryoid body aggregates consisting both of differentiated and undifferentiated cells as revealed at the ultrastructural evaluation. It is concluded that the isolated palatal MSCs fulfilled the basic criteria defining the stem cells. This new source of stem cells characterized here for the first time opens new perspectives on possible applications in basic research and in regenerative medicine.
This paper reviews the progress in the rapidly expanding scientific discipline of tissue engineering, which may have an integral role in the future of otorhinolaryngology. This article seeks to inform on the current concepts and principles of tissue engineering, and describe the state of the art research and developments in this exciting field as applied to ENT and head and neck surgery.
In order to carry out a comprehensive review of the literature spanning the past 30 years, a search of relevant publications was performed using the Web of Knowledge, Medline and PubMed databases.
This search identified 85 scholarly articles, which were utilised as the basis of this review.
Given the current rate of development of tissue engineering research, it is likely that tissue-engineered implants will be widely used in surgical practice, including ENT and head and neck surgery.
In the management of sensorineural hearing loss, effective therapy for degenerated hair cells, third order neurons, ganglions, dendrites and synaptic areas of the vestibulo-cochleo-cerebral pathway remains an enigma. Transplantation of stem and progenitor cells appears to be an emerging potential solution, and is the focus of this review.
To review recent developments in the management of sensorineural hearing loss in the field of stem cell research.
Materials and method:
A systematic review of the English language literature included all experimental and non-experimental studies with a Jadad score of three or more, published between 2000 and 2010 and included in the following databases: Cochrane Library Ear, Nose and Throat Disorders; Medline; Google Scholar; Hinari; and the Online Library of Toronto University.
Of the 455 and 29 600 articles identified from Medline and Google Scholar, respectively, 48 met the inclusion criteria. These were independently reviewed and jointly analysed.
Although there is not yet any evidence from successful human studies, stem cell and ‘alternative stem cell’ technology seems to represent the future of sensorineural hearing loss management.
There is evidence that cancer develops when cells acquire a sequence of mutations that
alter normal cell characteristics. This sequence determines a hierarchy among the cells,
based on how many more mutations they need to accumulate in order to become cancerous.
When cells divide, they exhibit telomere loss and differentiate, which defines another
cell hierarchy, on top of which is the stem cell. We propose a mutation-generation model,
which combines the mutation-accumulation hierarchy with the differentiation hierarchy of
the cells, allowing us to take a step further in examining cancer development and growth.
The results of the model support the hypothesis of the cancer stem cell’s role in cancer
pathogenesis: a very small fraction of the cancer cell population is responsible for the
cancer growth and development. Also, according to the model, the nature of mutation
accumulation is sufficient to explain the faster growth of the cancer cell population.
However, numerical results show that in order for a cancer to develop within a reasonable
time frame, cancer cells need to exhibit a higher proliferation rate than normal
Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. In this review, we provide an overview of current knowledge of MaSC gained from studies using mouse and human model systems and present research on bovine MaSC within that context. Recent data indicate that MaSC retain labeled DNA for extended periods because of their selective segregation of template DNA strands during mitosis. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC. These label-retaining epithelial cells (LREC) are in low abundance within mammary epithelium (<1%). They are predominantly estrogen receptor (ER)-negative and localized in a basal or suprabasal layer of the epithelium throughout the gland. Thus, the response of MaSC to estrogen, the major mitogen in mammary gland, is likely mediated by paracrine factors released by cells that are ER-positive. This is consistent with considerable evidence for cross-talk within and between epithelial cells and surrounding stromal cells. Excision of classes of cells by laser microdissection and subsequent microarray analysis will hopefully provide markers for MaSC and insights into their regulation. Preliminary analyses of gene expression in laser-microdissected LREC and non-LREC are consistent with the concept that LREC represent populations of stem cells and progenitor cells that differ with regard to their properties and location within the epithelial layer. We have attempted to modulate the MaSC number by infusing a solution of xanthosine through the teat canal and into the ductal network of the mammary glands of prepubertal heifers. This treatment increased the number of putative stem cells, as evidenced by an increase in the percentage of LREC and increased telomerase activity within the tissue. The exciting possibility that stem cell expansion can influence milk production is currently under investigation.
The role of centrosomes in stem cell division has recently been highlighted and further ascribes important functions to centrosomes in stem cell maintenance, cellular differentiation, and development. Advanced cell and molecular studies coupled with immunofluorescence, electron microscopy, and live cell imaging of specific centrosome proteins have contributed greatly to our knowledge of centrosome composition, structure, and dynamics and have uncovered new insights into mechanisms of centrosome functions in asymmetric cell division. The establishment of asymmetry and differential positioning of mother and daughter centrosomes during stem cell mitosis is important for allowing one cell to maintain stem cell characteristics while the sibling cell undergoes differentiation. Another key role for centrosomes has been revealed in primary cilia of embryonic stem cells that play significant roles in cellular signaling and are therefore critically important for stem cell decisions. Studies of signaling through primary cilia may contribute important information that may aid in the production of specific cells that are suitable for tissue repair and regeneration in the field of regenerative medicine.
To investigate whether artificial perilymph can induce neural stem cells, derived from the hippocampus of newborn guinea pigs, to differentiate into inner ear hair cells, in vitro.
Primary neural stem cells derived from the hippocampus of newborn guinea pigs were incubated in medium containing either 10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for three weeks. Differentiated cells were identified using immunofluorescence, Western blot and scanning electron microscopy.
Both fetal bovine serum and artificial perilymph induced the neural stem cells to differentiate into cells with hair-cell-specific antibodies.
Neural stem cells can survive in both fetal bovine serum and artificial perilymph, and within these media can differentiate into cells with hair-cell-specific antibodies. This provides an experimental basis for transplantation of neural stem cells into the inner ear.
To investigate whether hair cell immunophenotypes can be derived from the central nervous system.
We established in vitro cell cultures from embryonic day 14.5 fetal rat brain tissue, and analysed changes in the immunohistochemical features of these cell cultures following differentiation.
The immature neural progenitors obtained from the fetal mouse central nervous system generated cell immunophenotypes which expressed epitopes of the hair cell marker proteins myosin VIIa and Brn-3c and the supporting cell marker pan-cytokeratin.
Neural progenitors have the potential to differentiate into inner ear hair cell and supporting cell phenotypes, and thus may be a useful material for cell transplantation therapy aiming to replace damaged inner ear hair cells.
Stem cells are a potential means of tissue regeneration in the brain that hold promise for treatment of the large number of stroke survivors who have permanent disability. Animal studies with stem cells derived from many different sources indicate that cells can migrate to the site of ischaemic injury in the brain, and that some survive and differentiate into neurones and glia with evidence of electrical function. Cells additionally promote endogenous repair mechanisms, including mobilization of neural stem cells resident within the adult brain. Whether the behavioural benefits seen with stem cell administration in rodent models reflect enhanced endogenous recovery or tissue regeneration is unclear. Production of stem cells to clinical standards and in quantities required for clinical studies is technically challenging. To date only a handful of patients have been involved in preliminary clinical studies of cell therapies for stroke, and there are therefore insufficient data to draw conclusions about either safety or efficacy. Further trials with several cell types are ongoing or planned, including neural stem cells, and bone marrow-derived stem cells and endothelial progenitor cells.
Almost half of the children with symptomatic dilated cardiomyopathy receive a transplant or die within 2 years; however, cardiac stem cell transplantation has become a promising therapeutic option. The present case demonstrates for the first time, to our knowledge, the intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill 4-month-old child with severe dilated cardiomyopathy. Left ventricular ejection fraction increased from 20% before stem cell transplantation to 41% at 4 months of follow-up.
Detection and tracking of stem cell state are difficult due to insufficient means for rapidly screening cell state in a noninvasive manner. This challenge is compounded when stem cells are cultured in aggregates or three-dimensional (3D) constructs because living cells in this form are difficult to analyze without disrupting cellular contacts. Multiphoton laser scanning microscopy is uniquely suited to analyze 3D structures due to the broad tunability of excitation sources, deep sectioning capacity, and minimal phototoxicity but is throughput limited. A novel multiphoton fluorescence excitation flow cytometry (MPFC) instrument could be used to accurately probe cells in the interior of multicell aggregates or tissue constructs in an enhanced-throughput manner and measure corresponding fluorescent properties. By exciting endogenous fluorophores as intrinsic biomarkers or exciting extrinsic reporter molecules, the properties of cells in aggregates can be understood while the viable cellular aggregates are maintained. Here we introduce a first generation MPFC system and show appropriate speed and accuracy of image capture and measured fluorescence intensity, including intrinsic fluorescence intensity. Thus, this novel instrument enables rapid characterization of stem cells and corresponding aggregates in a noninvasive manner and could dramatically transform how stem cells are studied in the laboratory and utilized in the clinic.
Glial progenitor cells (GPCs) comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for central nervous system (CNS) remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand–receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.